AU2019393162A1 - Pharmaceutical compounds and their use as inhibitors of Ubiquitin Specific Protease 19 (USP19) - Google Patents

Info

Publication number

AU2019393162A1

AU2019393162A1 AU2019393162A AU2019393162A AU2019393162A1 AU 2019393162 A1 AU2019393162 A1 AU 2019393162A1 AU 2019393162 A AU2019393162 A AU 2019393162A AU 2019393162 A AU2019393162 A AU 2019393162A AU 2019393162 A1 AU2019393162 A1 AU 2019393162A1

Authority

AU

Australia

Prior art keywords

methyl

hydroxy

azaspiro

decan

carbonyl

Prior art date

2018-12-06

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 341
• 101000644843 Homo sapiens Ubiquitin carboxyl-terminal hydrolase 19 Proteins 0.000 title claims abstract description 171
• 102100020728 Ubiquitin carboxyl-terminal hydrolase 19 Human genes 0.000 title claims abstract description 170
• 239000003112 inhibitor Substances 0.000 title claims abstract description 93
• 238000000034 method Methods 0.000 claims abstract description 286
• 201000000585 muscular atrophy Diseases 0.000 claims abstract description 43
• 208000008589 Obesity Diseases 0.000 claims abstract description 31
• 235000020824 obesity Nutrition 0.000 claims abstract description 31
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 177
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 116
• 125000003118 aryl group Chemical group 0.000 claims description 107
• 150000003839 salts Chemical class 0.000 claims description 100
• 125000001072 heteroaryl group Chemical group 0.000 claims description 91
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 85
• -1 cyclopropyloxy, phenyl Chemical group 0.000 claims description 85
• 229910052799 carbon Inorganic materials 0.000 claims description 73
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 72
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 67
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 58
• 125000005843 halogen group Chemical group 0.000 claims description 58
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 56
• 229910052757 nitrogen Inorganic materials 0.000 claims description 51
• 125000004043 oxo group Chemical group O=* 0.000 claims description 50
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 47
• 239000008194 pharmaceutical composition Substances 0.000 claims description 47
• 125000000623 heterocyclic group Chemical group 0.000 claims description 46
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 45
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 43
• 125000005842 heteroatom Chemical group 0.000 claims description 43
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 41
• 206010022489 Insulin Resistance Diseases 0.000 claims description 38
• 206010028980 Neoplasm Diseases 0.000 claims description 34
• 201000011510 cancer Diseases 0.000 claims description 32
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 31
• DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 28
• 125000001424 substituent group Chemical group 0.000 claims description 28
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 26
• 125000001931 aliphatic group Chemical group 0.000 claims description 23
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 22
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
• 229910052717 sulfur Inorganic materials 0.000 claims description 21
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 20
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 19
• 150000001336 alkenes Chemical class 0.000 claims description 18
• 150000001345 alkine derivatives Chemical class 0.000 claims description 18
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 18
• 210000003205 muscle Anatomy 0.000 claims description 18
• 125000004193 piperazinyl group Chemical group 0.000 claims description 18
• 125000004076 pyridyl group Chemical group 0.000 claims description 18
• 229910052705 radium Inorganic materials 0.000 claims description 18
• 229910052701 rubidium Inorganic materials 0.000 claims description 18
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 17
• GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 16
• 229910052801 chlorine Inorganic materials 0.000 claims description 15
• 229910003827 NRaRb Inorganic materials 0.000 claims description 14
• 125000003368 amide group Chemical group 0.000 claims description 14
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 14
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 13
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical class C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 12
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 10
• 229910052731 fluorine Inorganic materials 0.000 claims description 10
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 10
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
• 125000003386 piperidinyl group Chemical group 0.000 claims description 9
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 9
• HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 claims description 8
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 8
• 229910052794 bromium Inorganic materials 0.000 claims description 8
• 125000004212 difluorophenyl group Chemical group 0.000 claims description 8
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 8
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
• 125000006519 CCH3 Chemical group 0.000 claims description 7
• YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
• 229910052760 oxygen Inorganic materials 0.000 claims description 7
• 150000003235 pyrrolidines Chemical class 0.000 claims description 7
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 7
• UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical group C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 claims description 6
• 101100167062 Caenorhabditis elegans chch-3 gene Chemical group 0.000 claims description 6
• VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 claims description 6
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
• 125000001544 thienyl group Chemical group 0.000 claims description 6
• 125000005505 thiomorpholino group Chemical group 0.000 claims description 6
• 229930192474 thiophene Chemical class 0.000 claims description 6
• 229910052739 hydrogen Inorganic materials 0.000 claims description 5
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 5
• HYSXDBRDXTYCJF-PHSANKKPSA-N 1-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]piperazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C(CNCC1)=O)C HYSXDBRDXTYCJF-PHSANKKPSA-N 0.000 claims description 4
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• JSAFIRHPPSSGEY-YDONVPIESA-N 4-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-5-oxopyrazine-2-carboxylic acid Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=C(N=CC1=O)C(=O)O)C JSAFIRHPPSSGEY-YDONVPIESA-N 0.000 claims description 4
• JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 4
• 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 4
• 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 4
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 4
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 4
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
• SGTNKBWTSZHULO-ACVCQEAVSA-N 1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-5-pyridin-2-ylpyrazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1C(C=NC(=C1)C1=NC=CC=C1)=O)(C)C)C SGTNKBWTSZHULO-ACVCQEAVSA-N 0.000 claims description 3
• HZOMVNLYYFCUCI-PLEWWHCXSA-N 1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]pyrazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1C(C=NC=C1)=O)(C)C)C HZOMVNLYYFCUCI-PLEWWHCXSA-N 0.000 claims description 3
• IFRABRQGODDNEK-DDAUYOFQSA-N 1-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-4-phenylpiperazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C(CN(CC1)C1=CC=CC=C1)=O)C IFRABRQGODDNEK-DDAUYOFQSA-N 0.000 claims description 3
• OKCYPTCUWWPHEL-PHSANKKPSA-N 1-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]pyrazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C(C=NC=C1)=O)C OKCYPTCUWWPHEL-PHSANKKPSA-N 0.000 claims description 3
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 3
• QEJAOARLVYCDKT-HXUWFJFHSA-N 4-(2-fluorophenyl)-1-[[4-hydroxy-1-[(3R)-3-phenylbutanoyl]piperidin-4-yl]methyl]piperazin-2-one Chemical compound FC1=C(C=CC=C1)N1CC(N(CC1)CC1(CCN(CC1)C(C[C@@H](C)C1=CC=CC=C1)=O)O)=O QEJAOARLVYCDKT-HXUWFJFHSA-N 0.000 claims description 3
• AKKUIUIKBXMSHO-PHSANKKPSA-N 4-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]morpholin-3-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C(COCC1)=O)C AKKUIUIKBXMSHO-PHSANKKPSA-N 0.000 claims description 3
• JFFOWRORFIMNFW-QFADGXAASA-N 5-chloro-1-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]pyrazin-2-one Chemical compound ClC=1N=CC(N(C=1)CC1(CCN(CC11CCCC1)C([C@@H](CC1CCCCC1)C)=O)O)=O JFFOWRORFIMNFW-QFADGXAASA-N 0.000 claims description 3
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
• CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 claims description 3
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
• 150000003053 piperidines Chemical class 0.000 claims description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 2
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 2
• ACGCKKFDHOSQAW-IHKRANBOSA-N 1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-5-phenylpyrazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1C(C=NC(=C1)C1=CC=CC=C1)=O)(C)C)C ACGCKKFDHOSQAW-IHKRANBOSA-N 0.000 claims description 2
• QQAXUAWTDUFGAK-ACVCQEAVSA-N 1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-5-pyridin-3-ylpyrazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1C(C=NC(=C1)C=1C=NC=CC=1)=O)(C)C)C QQAXUAWTDUFGAK-ACVCQEAVSA-N 0.000 claims description 2
• XXUIUVZONKBVMH-ACVCQEAVSA-N 1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-5-pyridin-4-ylpyrazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1C(C=NC(=C1)C1=CC=NC=C1)=O)(C)C)C XXUIUVZONKBVMH-ACVCQEAVSA-N 0.000 claims description 2
• CCLYJVUTERSNAN-CHQVSRGASA-N 1-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-3-methylpyrazin-2-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C(C(=NC=C1)C)=O CCLYJVUTERSNAN-CHQVSRGASA-N 0.000 claims description 2
• ZPSWWIWUPXDTTJ-CHQVSRGASA-N 1-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-5-methylpyrazin-2-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C(C=NC(=C1)C)=O ZPSWWIWUPXDTTJ-CHQVSRGASA-N 0.000 claims description 2
• GKDNSUPLHLPVFM-OVCWQMANSA-N 1-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4,6-dimethylazepan-2-one Chemical compound C[C@H](CC(F)(F)F)C(=O)N1CCC(O)(CN2CC(C)CC(C)CC2=O)C2(CCCC2)C1 GKDNSUPLHLPVFM-OVCWQMANSA-N 0.000 claims description 2
• PYWSEKHDBZGLEC-IMHYJWESSA-N 1-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4-phenylazetidin-2-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C(CC1C1=CC=CC=C1)=O PYWSEKHDBZGLEC-IMHYJWESSA-N 0.000 claims description 2
• IUZIHROWZTYWJJ-PHSANKKPSA-N 1-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-4-phenylpiperazin-2-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C(CN(CC1)C1=CC=CC=C1)=O IUZIHROWZTYWJJ-PHSANKKPSA-N 0.000 claims description 2
• SIRURBCLDOHPJN-IKJXHCRLSA-N 1-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]pyrazin-2-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C(C=NC=C1)=O SIRURBCLDOHPJN-IKJXHCRLSA-N 0.000 claims description 2
• QIRUORNHNYFGHQ-PLEWWHCXSA-N 1-[[7-[(2R)-3-cyclobutyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]pyrazin-2-one Chemical compound C1(CCC1)C[C@H](C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C(C=NC=C1)=O)C QIRUORNHNYFGHQ-PLEWWHCXSA-N 0.000 claims description 2
• KPDMSAOBHKTRJG-VGOKPJQXSA-N 1-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-4-methylpiperazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C(CN(CC1)C)=O)C KPDMSAOBHKTRJG-VGOKPJQXSA-N 0.000 claims description 2
• ANFKEQGMHROFEU-HFLPEKOISA-N 1-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]indole-2,3-dione Chemical compound C[C@H](CC1CCCCC1)C(=O)N1CCC(O)(CN2C(=O)C(=O)c3ccccc23)C2(CCCC2)C1 ANFKEQGMHROFEU-HFLPEKOISA-N 0.000 claims description 2
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
• ZJCDVLYPVQSKOK-UHFFFAOYSA-N 2-[[1-(3-cyclohexyl-2-methylpropanoyl)-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-2-azaspiro[4.5]decan-3-one Chemical compound C1(CCCCC1)CC(C(=O)N1CC(C(CC1)(O)CN1CC2(CC1=O)CCCCC2)(C)C)C ZJCDVLYPVQSKOK-UHFFFAOYSA-N 0.000 claims description 2
• VDJHUEGGIOZJMI-QFADGXAASA-N 2-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-[1,2,4]triazolo[4,3-a]pyridin-3-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC(C(CC1)(O)CN1N=C2N(C=CC=C2)C1=O)(C)C)C VDJHUEGGIOZJMI-QFADGXAASA-N 0.000 claims description 2
• DRPFRXFYHKAHFP-SMFUYQKNSA-N 2-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6,7-dimethoxyisoquinolin-1-one Chemical compound COc1cc2ccn(CC3(O)CCN(CC33CCCC3)C(=O)[C@H](C)CC(F)(F)F)c(=O)c2cc1OC DRPFRXFYHKAHFP-SMFUYQKNSA-N 0.000 claims description 2
• NOIXNOMHHWGUTG-UHFFFAOYSA-N 2-[[4-[4-pyridin-4-yl-1-(2,2,2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline Chemical compound C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C1=NN(CC(F)(F)F)C=C1C1=CC=NC=C1 NOIXNOMHHWGUTG-UHFFFAOYSA-N 0.000 claims description 2
• QGSBFNGNCGMASB-IHKRANBOSA-N 2-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-3H-isoindol-1-one Chemical compound C[C@H](CC1CCCCC1)C(=O)N1CCC(O)(CN2Cc3ccccc3C2=O)C2(CCCC2)C1 QGSBFNGNCGMASB-IHKRANBOSA-N 0.000 claims description 2
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• MOALONAATLYMTL-BWDMCYIDSA-N 4-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]morpholin-3-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C(COCC1)=O MOALONAATLYMTL-BWDMCYIDSA-N 0.000 claims description 2
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• ADVLUCPOUAYXLR-IWPPFLRJSA-N 4-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-7-oxa-4-azaspiro[2.5]octan-5-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C2(CC2)COCC1=O ADVLUCPOUAYXLR-IWPPFLRJSA-N 0.000 claims description 2
• WLNMSUKBWGNAMH-IKJXHCRLSA-N 4-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]morpholin-3-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C(COCC1)=O WLNMSUKBWGNAMH-IKJXHCRLSA-N 0.000 claims description 2
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• ANPGXNFXNIYUNL-OEPVSBQMSA-N 4-benzoyl-1-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]piperazin-2-one Chemical compound C(C1=CC=CC=C1)(=O)N1CC(N(CC1)CC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)O)=O ANPGXNFXNIYUNL-OEPVSBQMSA-N 0.000 claims description 2
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• SHYBXVRKUQSDHT-UHFFFAOYSA-N 4-benzyl-1-[[1-(3-cyclohexylpropanoyl)-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]pyrrolidin-2-one Chemical compound C(C1=CC=CC=C1)C1CC(N(C1)CC1(C(CN(CC1)C(CCC1CCCCC1)=O)(C)C)O)=O SHYBXVRKUQSDHT-UHFFFAOYSA-N 0.000 claims description 2
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• KHFQPEUSVHBHRR-ABYGYWHVSA-N 4-cyclopropyl-1-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]pyridin-2-one Chemical compound C1(CC1)C1=CC(N(C=C1)C[C@@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)O)=O KHFQPEUSVHBHRR-ABYGYWHVSA-N 0.000 claims description 2
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• 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 claims description 2
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• RWSBAEGPHNKMFD-DPBCKWEASA-N 1-[[(4R)-1-[(2S)-2-(cyclohexylmethyl)-3-hydroxypropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-N,N-dimethyl-6-oxo-4-phenylpiperidine-3-carboxamide Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC([C@@](CC1)(O)CN1CC(C(CC1=O)C1=CC=CC=C1)C(=O)N(C)C)(C)C)CO RWSBAEGPHNKMFD-DPBCKWEASA-N 0.000 claims 1
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• FVCUOKNOJLCAMA-QYWNIODHSA-N 1-[[1-[(2R)-3-cyclohexyl-2-methylpropanoyl]-4-hydroxy-3,3-dimethylpiperidin-4-yl]methyl]-5-indazol-1-ylpyrazin-2-one Chemical compound C1=CC=C2N(N=CC2=C1)C=1N=CC(=O)N(C=1)CC1(C(C)(CN(C(=O)[C@@H](CC2CCCCC2)C)CC1)C)O FVCUOKNOJLCAMA-QYWNIODHSA-N 0.000 claims 1
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• GJLKAAJOLACHGP-VGOKPJQXSA-N 1-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-4-methylsulfonylpiperazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C(CN(CC1)S(=O)(=O)C)=O)C GJLKAAJOLACHGP-VGOKPJQXSA-N 0.000 claims 1
• QFHNCRDRHYNUOZ-IFIVVKAWSA-N 1-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-5-methylsulfanyl-4-phenylpyridin-2-one Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C=C1SC)CC1(C2(CCCC2)CN(CC1)C(=O)[C@@H](CC1CCCCC1)C)O QFHNCRDRHYNUOZ-IFIVVKAWSA-N 0.000 claims 1
• ZLGJTNWIWCPEOL-DMDVIOLWSA-N 1-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-5-pyridin-4-ylpyrazin-2-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C(C=NC(=C1)C1=CC=NC=C1)=O)C ZLGJTNWIWCPEOL-DMDVIOLWSA-N 0.000 claims 1
• NVVUEALHSRUMPQ-YCIOTGQKSA-N 1-benzyl-5-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C(C1=CC=CC=C1)N1N=CC2=C1N=CN(C2=O)CC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)O NVVUEALHSRUMPQ-YCIOTGQKSA-N 0.000 claims 1
• GQVIJTAZMUXDKH-UHFFFAOYSA-N 1-methyl-6-methylsulfanyl-2h-pyrazolo[3,4-d]pyrimidin-3-one Chemical compound CSC1=NC=C2C(=O)NN(C)C2=N1 GQVIJTAZMUXDKH-UHFFFAOYSA-N 0.000 claims 1
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• VVRZDOSTELBVHV-GMMLNUAGSA-N 2-[[10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-2,7-naphthyridin-1-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C(C2=CN=CC=C2C=C1)=O VVRZDOSTELBVHV-GMMLNUAGSA-N 0.000 claims 1
• KMNYIHSPCMTVTC-XESZBRCGSA-N 2-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-2,7-naphthyridin-1-one Chemical compound OC1(CCN(CC11CCCC1)C([C@@H](CC(F)(F)F)C)=O)CN1C(C2=CN=CC=C2C=C1)=O KMNYIHSPCMTVTC-XESZBRCGSA-N 0.000 claims 1
• NEEMEKAPIDAUMM-RBFZIWAESA-N 2-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]-3H-pyrrolo[3,4-c]pyridin-1-one Chemical compound C[C@H](CC(F)(F)F)C(=O)N1CCC(O)(CN2Cc3cnccc3C2=O)C2(CCCC2)C1 NEEMEKAPIDAUMM-RBFZIWAESA-N 0.000 claims 1
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• DKAPBTKHGGMZAA-GMMLNUAGSA-N 2-[[10-hydroxy-7-[(3R)-3-phenylmorpholine-4-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-2,7-naphthyridin-1-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](COCC1)C1=CC=CC=C1)CN1C(C2=CN=CC=C2C=C1)=O DKAPBTKHGGMZAA-GMMLNUAGSA-N 0.000 claims 1
• SUALRKISEZBLPJ-IHKRANBOSA-N 2-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-2,7-naphthyridin-1-one Chemical compound C1(CCCCC1)C[C@H](C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C(C2=CN=CC=C2C=C1)=O)C SUALRKISEZBLPJ-IHKRANBOSA-N 0.000 claims 1
• SAXURKYCZMBYJL-SSEXGKCCSA-N 3-[[(10S)-10-hydroxy-7-(2-phenylpyrazolidine-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1N(CCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 SAXURKYCZMBYJL-SSEXGKCCSA-N 0.000 claims 1
• JEGKDJGLEZUCOZ-SLJLDQLWSA-N 3-[[(10S)-10-hydroxy-7-(3-phenylthiomorpholine-4-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC=CC=C1C1N(C(=O)N2CC[C@](CN3C(=O)C=C(C4=CC=CC=C4)N=C3)(O)C3(CCCC3)C2)CCSC1 JEGKDJGLEZUCOZ-SLJLDQLWSA-N 0.000 claims 1
• PVMMGYCTRFCPMW-XDFJSJKPSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-2-methyl-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@@](CNCC1)(C1=CC=CC=C1)C)CN1C=NC(=CC1=O)C1=CC=CC=C1 PVMMGYCTRFCPMW-XDFJSJKPSA-N 0.000 claims 1
• JDTFYUQQXUPFDM-GMCHKSTQSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-(2-methylphenyl)pyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=C(C=CC=C1)C JDTFYUQQXUPFDM-GMCHKSTQSA-N 0.000 claims 1
• DVYVKBNDOSWBKV-GMCHKSTQSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-(4-methoxyphenyl)pyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=CC=C(C=C1)OC DVYVKBNDOSWBKV-GMCHKSTQSA-N 0.000 claims 1
• DNPGSECSFMGKFR-GMCHKSTQSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-(4-methylphenyl)pyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=CC=C(C=C1)C DNPGSECSFMGKFR-GMCHKSTQSA-N 0.000 claims 1
• FTNDRPWYMUJHIP-BKMJKUGQSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-methylpyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C FTNDRPWYMUJHIP-BKMJKUGQSA-N 0.000 claims 1
• HSPUISMKFWJKHX-SETSBSEESA-N 3-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-piperidin-1-ylpyrimidin-4-one Chemical compound C1CCN(CC1)C2=CC(=O)N(C=N2)C[C@@]3(CCN(CC34CCCC4)C(=O)N5CCNC[C@H]5C6=CC=CC=C6)O HSPUISMKFWJKHX-SETSBSEESA-N 0.000 claims 1
• BTJVDDOXPAEGDX-PWUYWRBVSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-thiophen-2-ylpyrimidin-4-one Chemical compound C1CCC2(C1)CN(CC[C@]2(CN3C=NC(=CC3=O)C4=CC=CS4)O)C(=O)N5CCNC[C@H]5C6=CC=CC=C6 BTJVDDOXPAEGDX-PWUYWRBVSA-N 0.000 claims 1
• XTXCGZOHTADUHA-ABYGYWHVSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-thiophen-3-ylpyrimidin-4-one Chemical compound C1CCC2(C1)CN(CC[C@]2(CN3C=NC(=CC3=O)C4=CSC=C4)O)C(=O)N5CCNC[C@H]5C6=CC=CC=C6 XTXCGZOHTADUHA-ABYGYWHVSA-N 0.000 claims 1
• GAKARXLKXVKENF-SUYBVONHSA-N 3-[[(10S)-10-hydroxy-7-[(2R)-5-oxo-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNC(C1)=O)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 GAKARXLKXVKENF-SUYBVONHSA-N 0.000 claims 1
• MXTJOAKBZHOLMB-DLFZDVPBSA-N 3-[[(10S)-10-hydroxy-7-[(2S)-2-phenylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound O[C@]1(CCN(CC11CCCC1)C(=O)N1[C@H](CNCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 MXTJOAKBZHOLMB-DLFZDVPBSA-N 0.000 claims 1
• XOTPZXBJRXKSBO-JTSJOTPCSA-N 3-[[(10S)-10-hydroxy-7-[(2S)-2-phenylpyrrolidine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=C([C@H]2N(CCC2)C(=O)N2CC[C@](C3(CCCC3)C2)(CN2C(=O)C=C(C3=CC=CC=C3)N=C2)O)C=CC=C1 XOTPZXBJRXKSBO-JTSJOTPCSA-N 0.000 claims 1
• YFMPFSBIBBZIPZ-XMMPIXPASA-N 3-[[(10S)-10-hydroxy-7-[3-(trifluoromethyl)azetidine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(O)CCN(CC32CCCC3)C(=O)N2CC(C(F)(F)F)C2)C=N1 YFMPFSBIBBZIPZ-XMMPIXPASA-N 0.000 claims 1
• DZHWBWUTSHGSQV-GBAXHLBXSA-N 3-[[(10S)-10-hydroxy-7-[3-(trifluoromethyl)pyrrolidine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC=CC(=C1)C1=CC(=O)N(C[C@]2(O)CCN(CC32CCCC3)C(=O)N2CCC(C(F)(F)F)C2)C=N1 DZHWBWUTSHGSQV-GBAXHLBXSA-N 0.000 claims 1
• KUDMKGHATITQTL-SLJLDQLWSA-N 3-[[(10S)-7-(1,1-dioxo-3-phenyl-1,4-thiazinane-4-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC=CC=C1C1N(C(=O)N2CC[C@](C3(CCCC3)C2)(CN2C(=O)C=C(C3=CC=CC=C3)N=C2)O)CCS(=O)(=O)C1 KUDMKGHATITQTL-SLJLDQLWSA-N 0.000 claims 1
• UAIIRMPWNSOAID-GMCHKSTQSA-N 3-[[(10S)-7-[(2R)-2-(2,5-difluorophenyl)piperazine-1-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-(3-methylphenyl)pyrimidin-4-one Chemical compound FC1=C(C=C(C=C1)F)[C@H]1N(CCNC1)C(=O)N1CC2(CCCC2)[C@](CC1)(O)CN1C=NC(=CC1=O)C=1C=C(C=CC=1)C UAIIRMPWNSOAID-GMCHKSTQSA-N 0.000 claims 1
• DIWDFNQECFABMO-JTSJOTPCSA-N 3-[[(10S)-7-[(2R)-2-(3-fluorophenyl)piperazine-1-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound FC=1C=C(C=CC=1)[C@H]1N(CCNC1)C(=O)N1CC2(CCCC2)[C@](CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 DIWDFNQECFABMO-JTSJOTPCSA-N 0.000 claims 1
• AWAIVXFEKRZZPS-RYCFQHDISA-N 3-[[(10S)-7-[(2R)-4-acetyl-2-phenylpiperazine-1-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC([C@H]2N(C(=O)N3CC[C@@](CN4C(=O)C=C(C5=CC=CC=C5)N=C4)(C4(CCCC4)C3)O)CCN(C2)C(=O)C)=CC=C1 AWAIVXFEKRZZPS-RYCFQHDISA-N 0.000 claims 1
• HUYPEWSYXZZSSU-OBNYREETSA-N 3-[[(10S)-7-[(2S,4R)-4-amino-2-phenylpiperidine-1-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound N[C@H]1C[C@H](N(CC1)C(=O)N1CC2(CCCC2)[C@](CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1)C1=CC=CC=C1 HUYPEWSYXZZSSU-OBNYREETSA-N 0.000 claims 1
• HUYPEWSYXZZSSU-ZSHICZCASA-N 3-[[(10S)-7-[(2S,4S)-4-amino-2-phenylpiperidine-1-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound N[C@@H]1C[C@H](N(CC1)C(=O)N1CC2(CCCC2)[C@](CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1)C1=CC=CC=C1 HUYPEWSYXZZSSU-ZSHICZCASA-N 0.000 claims 1
• JATKNZZMWBFING-JTSJOTPCSA-N 3-[[(10S)-7-[(3R)-3-(2,5-difluorophenyl)-1,1-dioxo-1,4-thiazinane-4-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound FC1=C(C=C(C=C1)F)[C@H]1N(CCS(C1)(=O)=O)C(=O)N1CC2(CCCC2)[C@](CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 JATKNZZMWBFING-JTSJOTPCSA-N 0.000 claims 1
• JTBLBLKQMCPUPU-JTSJOTPCSA-N 3-[[(10S)-7-[(3R)-3-(2,5-difluorophenyl)thiomorpholine-4-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound FC1=C(C=C(C=C1)F)[C@H]1N(CCSC1)C(=O)N1CC2(CCCC2)[C@](CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 JTBLBLKQMCPUPU-JTSJOTPCSA-N 0.000 claims 1
• XLWVZLDIIACIBK-JTSJOTPCSA-N 3-[[(10S)-7-[(3R)-3-(4-fluorophenyl)morpholine-4-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC(=CC=C1[C@H]1N(C(=O)N2CC[C@](C3(CCCC3)C2)(CN2C(=O)C=C(C3=CC=CC=C3)N=C2)O)CCOC1)F XLWVZLDIIACIBK-JTSJOTPCSA-N 0.000 claims 1
• VGJBEEHVRFPCFB-SLJLDQLWSA-N 3-[[(10S)-7-[2-(2-fluorophenyl)piperazine-1-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound FC1=C(C=CC=C1)C1N(CCNC1)C(=O)N1CC2(CCCC2)[C@](CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 VGJBEEHVRFPCFB-SLJLDQLWSA-N 0.000 claims 1
• ISNRNUCXJVUDMF-SLJLDQLWSA-N 3-[[(10S)-7-[2-(3,4-difluorophenyl)piperazine-1-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound FC=1C=C(C=CC=1F)C1N(CCNC1)C(=O)N1CC2(CCCC2)[C@](CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 ISNRNUCXJVUDMF-SLJLDQLWSA-N 0.000 claims 1
• YREPWTLQMVUUDR-SLJLDQLWSA-N 3-[[(10S)-7-[2-(3,5-difluorophenyl)piperazine-1-carbonyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound FC=1C=C(C=C(C=1)F)C1N(CCNC1)C(=O)N1CC2(CCCC2)[C@](CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 YREPWTLQMVUUDR-SLJLDQLWSA-N 0.000 claims 1
• YLQHOBJQQVVXSW-UHFFFAOYSA-N 3-[[10-hydroxy-7-(2-oxa-5-azabicyclo[4.1.0]heptane-5-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C12OCCN(C2C1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 YLQHOBJQQVVXSW-UHFFFAOYSA-N 0.000 claims 1
• ZJHAGRRNQMSHTA-UHFFFAOYSA-N 3-[[10-hydroxy-7-(2-pyridin-4-ylpyrrolidine-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1C(CCC1)C1=CC=NC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 ZJHAGRRNQMSHTA-UHFFFAOYSA-N 0.000 claims 1
• UFPMXQGYGRXWRX-UHFFFAOYSA-N 3-[[10-hydroxy-7-(3-pyrrol-1-ylpyrrolidine-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound N1(C=CC=C1)C1CN(CC1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 UFPMXQGYGRXWRX-UHFFFAOYSA-N 0.000 claims 1
• APSZGYPTRPMABU-UHFFFAOYSA-N 3-[[10-hydroxy-7-(3-thiophen-2-ylmorpholine-4-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(Cn2cnc(cc2=O)-c2ccccc2)CCN(CC11CCCC1)C(=O)N1CCOCC1c1cccs1 APSZGYPTRPMABU-UHFFFAOYSA-N 0.000 claims 1
• GHTJUAUFEBJYCB-UHFFFAOYSA-N 3-[[10-hydroxy-7-(4-oxa-1-azaspiro[5.5]undecane-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1CCOCC11CCCCC1)CN1C=NC(=CC1=O)C1=CC=CC=C1 GHTJUAUFEBJYCB-UHFFFAOYSA-N 0.000 claims 1
• OSQKXKWCUVPKJP-UHFFFAOYSA-N 3-[[10-hydroxy-7-(7-oxa-1-azaspiro[3.4]octane-1-carbonyl)-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1CCC11COCC1)CN1C=NC(=CC1=O)C1=CC=CC=C1 OSQKXKWCUVPKJP-UHFFFAOYSA-N 0.000 claims 1
• PPCLIUCIULSXIK-TUHVGIAZSA-N 3-[[10-hydroxy-7-[(2R)-2-methylpiperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CNCC1)C)CN1C=NC(=CC1=O)C1=CC=CC=C1 PPCLIUCIULSXIK-TUHVGIAZSA-N 0.000 claims 1
• DPFVDOONKUFBGE-QMRFKDRMSA-N 3-[[10-hydroxy-7-[(2R)-4,4,4-trifluoro-2-methylbutanoyl]-7-azaspiro[4.5]decan-10-yl]methyl]thieno[2,3-d]pyrimidin-4-one Chemical compound C[C@H](CC(F)(F)F)C(=O)N1CCC(O)(Cn2cnc3sccc3c2=O)C2(CCCC2)C1 DPFVDOONKUFBGE-QMRFKDRMSA-N 0.000 claims 1
• SPTTYTGGUMNZPI-ZZDYIDRTSA-N 3-[[10-hydroxy-7-[(2S)-2-(1,2-oxazol-3-yl)pyrrolidine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CCC1)C1=NOC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 SPTTYTGGUMNZPI-ZZDYIDRTSA-N 0.000 claims 1
• JXGAMNKPXDSTFN-UHFKCPIBSA-N 3-[[10-hydroxy-7-[(2S)-2-(5-methyl-1H-1,2,4-triazol-3-yl)pyrrolidine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CCC1)C1=NNC(=N1)C)CN1C=NC(=CC1=O)C1=CC=CC=C1 JXGAMNKPXDSTFN-UHFKCPIBSA-N 0.000 claims 1
• ITKDJDKYYYTTCF-YJJLJQPASA-N 3-[[10-hydroxy-7-[(2S)-2-(thiophen-2-ylmethyl)pyrrolidine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1[C@@H](CCC1)CC=1SC=CC=1)CN1C=NC(=CC1=O)C1=CC=CC=C1 ITKDJDKYYYTTCF-YJJLJQPASA-N 0.000 claims 1
• GREJQRKDEWDODX-UHFFFAOYSA-N 3-[[10-hydroxy-7-[2-(2-methoxyphenyl)piperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1C(CNCC1)C1=C(C=CC=C1)OC)CN1C=NC(=CC1=O)C1=CC=CC=C1 GREJQRKDEWDODX-UHFFFAOYSA-N 0.000 claims 1
• DKDOUIBZLMOJRA-UHFFFAOYSA-N 3-[[10-hydroxy-7-[2-(4-methoxyphenyl)piperazine-1-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1C(CNCC1)C1=CC=C(C=C1)OC)CN1C=NC(=CC1=O)C1=CC=CC=C1 DKDOUIBZLMOJRA-UHFFFAOYSA-N 0.000 claims 1
• WKFVBZREXTWCSQ-UHFFFAOYSA-N 3-[[10-hydroxy-7-[3-(trifluoromethyl)morpholine-4-carbonyl]-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1C(COCC1)C(F)(F)F)CN1C=NC(=CC1=O)C1=CC=CC=C1 WKFVBZREXTWCSQ-UHFFFAOYSA-N 0.000 claims 1
• VFZYQVKRJBSERP-MLAKCTNMSA-N 3-[[5-hydroxy-2-[(2R)-2-phenylpiperazine-1-carbonyl]-2-azaspiro[5.5]undecan-5-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1=CC([C@H]2N(C(=O)N3CCC(CN4C(=O)C=C(C5=CC=CC=C5)N=C4)(C4(CCCCC4)C3)O)CCNC2)=CC=C1 VFZYQVKRJBSERP-MLAKCTNMSA-N 0.000 claims 1
• SVNVRTXCUPMVIY-MLAKCTNMSA-N 3-[[5-hydroxy-2-[(3R)-3-phenylmorpholine-4-carbonyl]-2-azaspiro[5.5]undecan-5-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCCC1)C(=O)N1[C@@H](COCC1)C1=CC=CC=C1)CN1C=NC(=CC1=O)C1=CC=CC=C1 SVNVRTXCUPMVIY-MLAKCTNMSA-N 0.000 claims 1
• HFQZBOGXDDBQAR-UHFFFAOYSA-N 3-[[7-(2-cyclobutylpiperazine-1-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(Cn2cnc(cc2=O)-c2ccccc2)CCN(CC11CCCC1)C(=O)N1CCNCC1C1CCC1 HFQZBOGXDDBQAR-UHFFFAOYSA-N 0.000 claims 1
• LDGQECQCSDVZBV-UHFFFAOYSA-N 3-[[7-(2-cyclopropylpyrrolidine-1-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound C1(CC1)C1N(CCC1)C(=O)N1CC2(CCCC2)C(CC1)(O)CN1C=NC(=CC1=O)C1=CC=CC=C1 LDGQECQCSDVZBV-UHFFFAOYSA-N 0.000 claims 1
• SCPZTQNBJZGVRM-UHFFFAOYSA-N 3-[[7-(3-cyclobutylmorpholine-4-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(Cn2cnc(cc2=O)-c2ccccc2)CCN(CC11CCCC1)C(=O)N1CCOCC1C1CCC1 SCPZTQNBJZGVRM-UHFFFAOYSA-N 0.000 claims 1
• IEGHOPASHKIVIS-UHFFFAOYSA-N 3-[[7-(5-azaspiro[2.5]octane-5-carbonyl)-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-6-phenylpyrimidin-4-one Chemical compound OC1(CCN(CC11CCCC1)C(=O)N1CC2(CC2)CCC1)CN1C=NC(=CC1=O)C1=CC=CC=C1 IEGHOPASHKIVIS-UHFFFAOYSA-N 0.000 claims 1
• MHMKGEHYRHSALS-DMDVIOLWSA-N 3-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]-8-methylquinazolin-4-one Chemical compound C[C@H](CC1CCCCC1)C(=O)N1CCC(O)(Cn2cnc3c(C)cccc3c2=O)C2(CCCC2)C1 MHMKGEHYRHSALS-DMDVIOLWSA-N 0.000 claims 1
• ANHPWTHKZJWFMA-ACVCQEAVSA-N 3-[[7-[(2R)-3-cyclohexyl-2-methylpropanoyl]-10-hydroxy-7-azaspiro[4.5]decan-10-yl]methyl]pyrido[4,3-d]pyrimidin-4-one Chemical compound C1CC2(C(CN3C(=O)C4=CN=CC=C4N=C3)(O)CCN(C2)C(=O)[C@@H](CC2CCCCC2)C)CC1 ANHPWTHKZJWFMA-ACVCQEAVSA-N 0.000 claims 1
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